The human immunodeficiency virus, HIV for short, belongs to the retrovirus family and to the lentivirus genus. An HIV infection when left untreated generally results in acquired immunodeficiency syndrome (AIDS) following a variably long incubation period, which typically takes several years. Over the past 30 years, the spread of HIV has evolved into a pandemic, which according to estimates of the UNAIDS organization has cost some 28 million lives so far. At the end of 2010, an estimated 34 million people worldwide were infected with HIV. With the exception of one isolated case that has been described, the disease is not curable as of yet and requires lifelong treatment, which suppresses the infection-related symptoms by inhibiting HIV replication.
According to the German-Austrian guidelines for antiretroviral therapy of HIV infection, the goal of antiretroviral therapies (ART) is to suppress infection-related symptoms and mitigate the progression of the disease by inhibiting HIV replication. The prognosis of patients infected with HIV can be considerably improved using highly active antiretroviral therapy (HAART). Patients today are achieving a relatively high age. The therapy, however, must be conducted for life since the viral infection is generally only suppressed, but not cured. The physical and mental stress resulting from the permanent need to take drugs and from an increased frequency of infections is high, as are the costs of years of HAART. While HAART lowers the risk of infection for HIV due to a reduced viral load, an infection cannot be avoided. It is therefore desirable to prevent infection.
The HI virus is transmitted via contact with body fluids such as blood, semen, vaginal secretion, and breast milk. The most common routes of infection are sex without the use of condoms and unsterile syringes during intravenous drug use. Despite the high significance of semen in the sexual transmission of HIV, little is known about the routes of transmission.
In 2007, amyloidogenic proteins contained in seminal fluid, referred to as semen-derived enhancer of virus infection (SEVI), were reported, which were able to amplify the HIV infection of various cell types in cell culture and tissue models. These potentially play an important role in the sexual transmission of HIV since they may facilitate the contact between the virus and the host cell (Münch et al., Cell 131, 1059-1071).
Conversely, it should be possible to prevent the sexual transmission of HIV by preventing SEVI-HIV cell interaction. Initial experimental approaches on the prevention of SEVI-mediated HIV infection through the use of amyloid-binding substances in cell culture were already presented (Capule et al., JACS 134, 905-908). Development has not yet progressed greatly.
D-peptides are known from the published prior art Sievers et al. (Nature (2011). 475, 96-100) which bind to a hexapeptide (residues 306-311) of the tau protein, which is associated with Alzheimer's disease. In addition, an L-peptide is known from this published prior art, which likewise binds to a hexapeptide of the 248PAP286 protein of human sperm. The respective fibril formation was able to be prevented specifically by way of the D-peptide for the tau protein, and by way of the L-peptide for the PAP protein.
Wojtowicz et al. In the year 2002 reported that synthetic, amyloid fibrils made up of Aβ1-40 and Aβ1-42 are able to enhance the infectivity of the HIV-1 virus (The Journal of Biological Chemistry (2002). 277, 35019-35024). Aβ fibrils result in a 5- to 20-fold increase in infection efficiency of reporter cells expressing the HIV-1 receptor CD4.